Syndecan-1, the most abundant heparan sulfate proteoglycan in the gastrointestinal tract, is reduced in the regenerative epithelium in inflammatory bowel disease (IBD). This study explored the effects of the immunomodulator glatiramer acetate (GA, Copaxon) treatment on syndecan-1 expression in dextran sodium sulphate (DSS) induced colitis. Acute and chronic colitis was induced in C57BL/6 mice by 2% and 1.5% DSS in tap water, respectively. GA was applied subcutaneously, 2 mg/mouse/day, starting on the day of DSS induction until the mice were sacrificed. Syndecan-1 expression was assessed by immunohistochemistry. The effect of adoptive transfer of GA-specific T-cells as an organ specific therapy and was also evaluated. Syndecan-1 expression was significantly lower in both colitis groups compared to naive mice (p<0.0001). GA attenuated clinical scores and pathological manifestations of colitis and led to reinstatement of normal levels of syndecan-1. Following adoptive transfer, GA specific cells homed to the surface epithelium of the distal colon, accompanied by augmentation of syndecan-1 staining in their vicinity. We concluded that syndecan-1 expression is reduced in DSS induced-colitis and could be a potential prognostic factor in IBD. Treatment with GA exerts not only an anti-inflammatory effect, but also a possible beneficial effect in stabilizing the intestinal epithelium barrier and tissue repair in DSS colitis. GA may be applied as a novel drug for IBD, shifting treatment from immunosupression towards immunomodulation..